Related Experiment Videos
[Severe hepatotoxicity of tuberculostatic agents. Increase in the incidence]
E Moitinho1, J M Salmerón, A Mas
1Servicio de Hepatologíe, Hospital Clinic i Provincial, Barcelona.
Abstract:
Hepatotoxicity by antituberculous drugs is well known. Nonetheless, severe liver involvement is infrequent. Several series of fulminant hepatitis by antituberculous drugs have recently been reported with a much greater frequency than previously reported. The present study describes the authors' experience which, similar to other groups, has shown a marked increase with respect to previous experience. During 1994 5 patients with acute severe hepatitis associated to antituberculous drugs were admitted to the authors' unit. The mean age of the patients was 43 years (range: 25-62). Two patients were healthy HBsAg carriers, one undergoing enzymatic inducer treatment and was anti-HIV positive. Another patient presented compensated liver cirrhosis by HCV. The 5 cases received combined isoniazid and rifampicin and four had also received pyrazinamide. Four patients presented hepatic encephalopathy. Of these cases, three could not undergo emergency liver transplantation because of contraindications and died due to complications of acute severe liver failure. Another patient evolved favorably following emergency liver transplantation. The only patient who presented good evolution with conservative treatment and who did not present hepatic encephalopathy had discontinued isoniazid because of the finding of slight hypertransaminasemia during a routine analytical control. Several risk factors have been reported for the appearance of hepatotoxicity by antituberculous drugs. The factor of greatest clinical importance for the development of severe hepatotoxicity is probably continuation of the treatment once hepatic dysfunction has initiated. The important increase in cases of severe toxicity urges the need for strict analytical monitoring following initiation of treatment.
Insights
Severe liver injury from antituberculous drugs is increasing. Close monitoring is crucial, as continuing treatment after liver dysfunction begins significantly raises the risk of fatal hepatotoxicity.
Area of Science:
- Hepatology
- Infectious Diseases
- Pharmacology
Background:
- Antituberculous drugs are known to cause liver damage.
- Severe hepatotoxicity, though infrequent, has seen a recent increase in reported cases.
- This study examines a recent surge in severe drug-induced liver injury.
Purpose of the Study:
- To report on a series of severe acute hepatitis cases linked to antituberculous drug use.
- To identify risk factors and emphasize the importance of monitoring.
- To highlight the clinical implications of increased hepatotoxicity frequency.
Main Methods:
- Retrospective analysis of 5 patients admitted with acute severe hepatitis.
- Review of patient demographics, medical history, drug regimens, and clinical outcomes.
- Assessment of risk factors, including pre-existing liver conditions and co-infections.
Main Results:
- Five patients (mean age 43) developed severe hepatitis from combined isoniazid, rifampicin, and pyrazinamide.
- Four patients had hepatic encephalopathy; three died due to liver failure.
- One patient survived via emergency liver transplantation; another improved with conservative management after isoniazid discontinuation.
- Continuation of treatment despite initial liver dysfunction was a key risk factor.
Conclusions:
- There is a concerning increase in severe hepatotoxicity from antituberculous drugs.
- Continuing treatment after signs of liver dysfunction is a critical risk factor for severe outcomes.
- Strict analytical monitoring is essential upon initiating antituberculous therapy to detect early signs of liver injury.